This invention relates to the use of N,N-dimethylglycine (DMG) to treat melanoma tumors in man or animals.
Dimethylglycine is an intermediary metabolite and amino acid found in low levels in many foods, and is produced in the body from choline. DMG is an endogenous compound and an enzyme system in the body effectively converts the substance into metabolites that are either used by the body or are safely excreted from the body.
A great deal of research has been carried out in recent years on the physiological effects of N,N-dimethylglycine.
Referring to previous work, U.S. Pat. No. 4,385,068, issued 5/24/83 discloses treating irradiated animals with a derivative of this compound to alleviate the effects of excess radiation on the immune system. The stated object of the invention of U.S. Pat. No. 4,385,068 is (a) to provide a method to enhance one or both of the cell-mediated response and humoral response of the body; (b) provide a method whereby the deliberately induced production of antibody artificially acquired in a living organism can be enhanced, and (c) to provide a method to increase the amount of antibody production and/or decrease the time of antibody production in the deliberately induced production of antibodies in a living organism. According to the patent, the DMG is administered so that the immunological response of the living organism is potentiated when exposed to an antigen in a natural environment and/or when deliberately exposed, or exposed to a subject after the subject has been exposed to a disease agent having an antigenic component in a natural environment in order to aid the host in responding to the naturally occurring infection.
The literature is also replete with articles concerning N,N-dimethylglycine and its potential uses.
At the 1980 Pacific Slope Biochemical Conference a paper entitled "Decrease of Lactic Acid Concentration in Blood of Animals Given N,N-Dimethylglycine" was presented. This research a the nutritional evaluation as a result of a 157-day subchronical estimation of N,N-dimethylglycine toxicity. This study also indicated that a decreased lactic acid production by male New Zealand white rabbits exposed to severe surgical stress by administering intravenously dimethylglycine. High-dose rats showed better adaptation to hypoxia subchronical toxicity tests.
In the January, 1981, issue of The Journal of Infectious Diseases, Vol. 143, No. 1, an article entitled "Immunomodulating Properties of Dimethylglycine in Humans", discussed the fact that dimethylglycine is an immunomodulator, if not an immunoadjuvant in humans (since the latter term is reserved for parenterally administered substances that are incorporated or injected simultaneously with an antigen). The normalization of mitogenic responsiveness by lymphocytes from patients with sickle cell disease and diabetes was tested. In both groups, the blast transformation activity of lymphocytes treated with DMG and exposed to three lectins was approximately doubled. Preliminary data suggest, according to the authors, that DMG is both a humoral and cellular immunomodulator, and might have great use with vaccines for intracellular infections and certain parasitic diseases. The article also states, "In addition, it should be tested for its effects on spontaneously occurring tumors in animals in which many of the immune parameters influencing tumor growth are known. Because DMG is nontoxic and can be given orally, it would seem to have obvious advantages over the oil-in-water adjuvants now contemplated for use in patients with cancer in conjunction with tumor associated antigen vaccines." There is no suggestion of dosage ranges or mode of application for DMG or that it would actually be effective for the treatment of any particular type of tumor.
The March, 1982, issue of Equine Practice contains an article entitled "Effect of a Nutritional Supplement Containing N,N-Dimethylglycine (DMG) on the Racing Standardbred." This article discloses that research showed that DMG can increase oxygen utilization and thereby decrease lactic acid levels in animals under extreme stress. The article also discusses the finding that human tests indicated an increase in exhaustion time, and an enhancement of the body's immune response, both by increasing the antibody production and lymphocyte generation by the administration of DMG. The tests reported in this article indicated that the inclusion of DMG in the diet of the racing Standardbred is responsible for a lower blood lactic acid level following training. Trainers found the horses to be more aggressive, to have better appetites and attitudes and to recover faster from racing and training than the controls.
The November-December, 1982, issue of Canine Practice contains an article entitled "A Clinical Evaluation of N,N-Dimethylglycine (DMG) and Diisopropylammonium Dichloroacetate (DIPA) on the Performance of Racing Greyhounds".
This article summarized the biological reactions of dimethylglycine in three broad categories: Transmethylation, cellular respiration, and hepatic function. The study that was the subject of the article indicated that improvement in racing performance was found when greyhounds were given DMG, and also stated that they showed better recovery after races with less fatigue or muscle stiffness. Additional clinical applications of DMG, including exertional rhabdomyolysis (inflammatory change in the muscle fibers of the longissimus group), muscular cramp, and hepato-pathology were discussed.
In the February, 1987, issue of Let's Live Magazine, an article entitled "DIMETHYLGLYCINE UPDATE, New Studies Confirm DMG Improves Health" states that the benefit of enhanced immunity is protection against diseases ranging from cancer and AIDS to minor diseases such as influenza. The article states that DMG is a metabolic enhancer, acts as a detoxifying agent and antioxidant, and is a versatile normalizer of physiological functions. The article also discusses the fact that the immune system is a complex network of white blood cells and molecular compounds, such as antibodies and interferon. There are two types of white blood cells--lymphocytes and macrophages. The immune system produces three types of lymphocytes: T cells, B cells, and K cells. Interferon is an antiviral, antitumor compound produced from T cells. The article indicates that T cells identify and reject foreign matter, while B cells produce antibodies. The article states that little is understood about the killer K cells, which can attack tumor cells directly. The article further states that early research showed that DMG stimulates B cells to produce much higher antibody responses (humoral branch) and potentiates the activity of T cells and macrophages (cellular immunity branch).
The article also states that the DMG was effective in doubling interferon production, and that further work is underway to evaluate DMG's effect on K cells, the body's principal defense mechanism against tumor cells. The article also alludes to a related line of research which indicated that the methyl-group donating ability of DMG is protective against cancer. As stated by the author, "I have already discussed the fact that DMG is not mutagenic or carcinogenic but, rather, is actually protective against mutagens and cancer."
In the February, 1987, issue of Health Consciousness, an article entitled "N,N-Dimethylglycine and the Immune Response" reviewed the prior research in the effect of DMG on the body, and also indicated that DMG will increase interferon production. The article states that DMG is an oral immune stimulating nutrient which can offer individuals increased resistance to and recovery from infectious diseases, and stated that depressed immunity is associated with most degenerative diseases such as cancer, diabetes and cardiovascular disease.
At the 1987 ASM Annual Meeting, a paper entitled "The Effect of DMG on the Immune Response of Rabbits" was presented. This paper concluded that DMG can affect the cellular branch of the immune system by lymphocyte activation. Lymphocytes from DMG fed animals can stimulate the cellular immune system by lymphatic proliferation. During primary response, high levels of interferon was present in the DMG fed animals, regardless of the immunogen source. No interferon was detected in immunized control animals not fed DMG. Interferon was not present in samples obtained following the secondary response.
In an article entitled "DMG, Properties and Proprieties" published in The Blood Horse on June 27, 1987, research on humans was discussed which showed that DMG stimulated B-cells produce much higher antibody responses and that it also enhances the activity of T cells and macrophages.
It has now been found that DMG is an effective agent for the treatment of tumors, particularly the prevention of the metastasis of melanoma tumors.